Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
Mol Med Rep. 2020 Mar;21(3):1461-1470. doi: 10.3892/mmr.2020.10953. Epub 2020 Jan 20.
The present study was designed to elucidate the underlying mechanisms of Bao Gui capsule (BGC) against hyperandrogenism, insulin resistance and leptin resistance of PCOS. Letrozole was used to induce a PCOS model in rats, which were then randomly divided into four groups (n=9): Control, Model, high‑dose BGC (BGC‑H) and low‑dose BGC (BGC‑L) group. Serum levels of follicle‑stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2), insulin, leptin, and interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α (TNF‑α) in the hypothalamus were determined by ELISA. Protein levels of cytochrome P450c17α and cytochrome P450 aromatase (P450arom) in ovaries were determined by immunohistochemistry and western blot analysis. Additionally, the expression of GLUT4 in uterus and muscle tissue, and NF‑κB, IKKβ and SOCS3 mRNA levels in the hypothalamus were evaluated. BGC significantly reduced body weight gain and decreased serum levels of LH/FSH, T, log T/E2, insulin and leptin compared with the PCOS model rats. Furthermore, BGC markedly reduced the expression of P450c17α and significantly increased the expression of P450arom in ovaries, and increased the expression of GLUT4 in uterus and muscle tissues. BGC also effectively reduced the level of IL‑6 and TNF‑α, and the expression of IKKβ, NF‑κB and SOCS3 in the hypothalamus of PCOS model rats. These results suggest that BGC may effectively improve hyperandrogenism, insulin resistance, endometrial receptivity and the low‑grade chronic inflammation in the hypothalamus.
本研究旨在阐明保胎胶囊(BGC)治疗多囊卵巢综合征(PCOS)高雄激素血症、胰岛素抵抗和瘦素抵抗的作用机制。采用来曲唑诱导大鼠 PCOS 模型,随机分为 4 组(n=9):对照组、模型组、高剂量 BGC(BGC-H)组和低剂量 BGC(BGC-L)组。采用 ELISA 法检测血清卵泡刺激素(FSH)、黄体生成素(LH)、睾酮(T)、雌二醇(E2)、胰岛素、瘦素及下丘脑白细胞介素(IL)-1β、IL-6 和肿瘤坏死因子-α(TNF-α)水平。采用免疫组化和 Western blot 分析检测卵巢细胞色素 P450c17α 和细胞色素 P450 芳香化酶(P450arom)蛋白水平。评价子宫和肌肉组织中 GLUT4 的表达以及下丘脑 NF-κB、IKKβ 和 SOCS3mRNA 水平。BGC 可显著降低 PCOS 模型大鼠体重增加,降低血清 LH/FSH、T、log T/E2、胰岛素和瘦素水平。此外,BGC 可显著降低卵巢 P450c17α 的表达,显著增加卵巢 P450arom 的表达,增加子宫和肌肉组织中 GLUT4 的表达。BGC 还可有效降低 PCOS 模型大鼠下丘脑 IL-6 和 TNF-α 水平,以及 IKKβ、NF-κB 和 SOCS3 的表达。这些结果表明,BGC 可有效改善 PCOS 患者的高雄激素血症、胰岛素抵抗、子宫内膜容受性和下丘脑低度慢性炎症。